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[e-drug] Contaminated Dextromethorphan active pharmaceutical ingredient

E-DRUG: Contaminated Dextromethorphan active pharmaceutical ingredient
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Drug Alert No. 129 

Contaminated Dextromethorphan active pharmaceutical ingredient
Background 
http://www.who.int/medicines/publications/drugalerts/App_Drug_Alert_No_129_
Paraguay_Dextro.pdf

On 24 January 2013 WHO Drug Alert number 126 was published following the
discovery in Pakistan of two types of locally produced cough syrups
containing the contaminated active pharmaceutical ingredient (API) 
Dextromethorphan. 

This led to the death of approximately 50 persons in Pakistan, all with a
history of drug addiction, who had been abusing dextromethorphan
containing syrups for many years without any reported unexpected adverse 
reactions. 

The subsequent investigation identified that both manufacturers in
Pakistan were obtaining Dextromethorphan API from Konduskar Laboratories
in India. 

Full laboratory testing of the Dextromethorphan showed that it was
contaminated with Levomethorphan, the enantiomer of Dextromethorphan,
which is a potent opioid analgesic internationally controlled under
schedule 1 of the single convention on Narcotic Drugs 1961.

In January 2013, as a result of this incident, the Indian Regulatory
authorities suspended the manufacture, distribution, sale or use of
Dextromethorphan by Konduskar Laboratories.

The WHO Drug Alert number 126 called on all countries to increase
vigilance for Dextromethorphan in general, and specifically if it had been
obtained from Konduskar Laboratories, to ensure that the API met all
required quality specifications.

Update 
On the 26 September 2013 WHO HQ were notified of suspected drug
intoxications involving 11 paediatric patients in Paraguay. All of the
patients were experiencing influenza-like symptoms and had consumed
medical products produced by a local manufacturer (INDUFAR C.S.I.A.)
containing Dextromethorphan. The children were aged between 2-9 years and
serious adverse reactions included altered consciousness, cyanosis,
respiratory distress, and seizures. The onset of symptoms occurred between
2-7 hours of ingesting the Dextromethorphan. 

Since then the number of patients experiencing adverse reactions has risen 
to 44 confirmed cases, and ranging in age from 5 months to 48 years. 
There has been one fatality that may be linked to this event.

The Paraguayan Ministry of Health has issued warnings concerning the
medicines thought to be connected to this incident. 

Page 2
Investigations by the Paraguayan authorities indicated the source of the
API Dextromethorphan, to be Konduskar Laboratories, India. The batch
number of the Dextromethorphan API manufactured by Konduskar and used by
the Paraguayan manufacturer was the same as one of the contaminated
batches found in Pakistan. However, the Paraguayan manufacturer appears to
have ordered the API from Konduskar in 2012, prior to the events in
Pakistan. 

According to the local manufacturer in Paraguay none of the products have
been exported, however it could possibly be available in neighbouring
countries through local traders and travellers.

WHO requests extra vigilance for the API Dextromethorphan in general, and
in particular that originating from Konduskar Laboratories, and strongly
advises that extreme caution should be exercised by importing countries
and manufacturers in determining that it is carefully tested for the
presence of the contaminant Levomethorphan, and meets the recognized
specifications. 

Samples of contaminated Dextromethorphan API from the original Pakistan
incident have been analysed at the request of WHO and revealed limits of
Levomethorphan varying between 9.5%-22.6%. 

All of the samples tested so
far in both incidents have failed to comply with the requirements for the
specific optical rotation as specified in the monograph for
Dextromethorphan hydrobromide published in The International Pharmacopeia
(see http://apps.who.int/phint/en/p/about/).

For any further information concerning this Alert, or if you have imported
Dextromethorphan from Konduskar Laboratories, India please contact
rapidalert@who.int. 

Carinne Bruneton <c.bruneton@remed.org>

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